奥地利维也纳医科大学Tibor Harkany研究团队绘制了下丘脑发育的分子图谱。该项研究成果于2020年5月6日在线发表于《自然》杂志。
研究人员结合外胚层来源的51199个小鼠细胞的单细胞RNA测序、基因调控网络（GRN）筛选以及基于全基因组关联研究的疾病表型和遗传谱系重建，来揭示了9个胶质细胞和33个神经亚型是由不同GRN控制下的中期妊娠产生。
从神经递质、神经肽和转录因子产生的组合分子代码对解码下丘脑神经元的分类学层次是极少需要的。γ-氨基丁酸（GABA）和多巴胺神经元（而不是谷氨酸神经元）的分化依赖于准稳定的中间状态，大量的GABA祖细胞产生多巴胺细胞。
研究人员发现了大量出乎意料的趋化性增殖和引导信号，通常与下丘脑的背侧（皮质）模式有关。特别是，SLIT-ROBO信号的缺失会损害脑室周围多巴胺神经元的产生和定位。
总体而言，这项研究确定了塑造下丘脑发育结构的分子原理，并展示了神经元异质性如何转化为多峰神经单元，从而在整个生命中提供了无限的自适应潜力。
据了解，下丘脑内有大量专门的神经内分泌命令系统，可控制脊椎动物最基本的生理需要。然而，整合了神经元和神经胶质多样性的分子决定因素以及下丘脑发育的时间和空间尺度的发育图谱仍缺乏。
附：英文原文
Title: Molecular design of hypothalamus development
Author: Roman A. Romanov, Evgenii O. Tretiakov, Maria Eleni Kastriti, Maja Zupancic, Martin Hring, Solomiia Korchynska, Konstantin Popadin, Marco Benevento, Patrick Rebernik, Francois Lallemend, Katsuhiko Nishimori, Frdric Clotman, William D. Andrews, John G. Parnavelas, Matthias Farlik, Christoph Bock, Igor Adameyko, Tomas Hkfelt, Erik Keimpema, Tibor Harkany
Issue&Volume: 2020-05-06
Abstract: A wealth of specialized neuroendocrine command systems intercalated within the hypothalamus control the most fundamental physiological needs in vertebrates1,2. Nevertheless, we lack a developmental blueprint that integrates the molecular determinants of neuronal and glial diversity along temporal and spatial scales of hypothalamus development3. Here we combine single-cell RNA sequencing of 51,199 mouse cells of ectodermal origin, gene regulatory network (GRN) screens in conjunction with genome-wide association study-based disease phenotyping, and genetic lineage reconstruction to show that nine glial and thirty-three neuronal subtypes are generated by mid-gestation under the control of distinct GRNs. Combinatorial molecular codes that arise from neurotransmitters, neuropeptides and transcription factors are minimally required to decode the taxonomical hierarchy of hypothalamic neurons. The differentiation of γ-aminobutyric acid (GABA) and dopamine neurons, but not glutamate neurons, relies on quasi-stable intermediate states, with a pool of GABA progenitors giving rise to dopamine cells4. We found an unexpected abundance of chemotropic proliferation and guidance cues that are commonly implicated in dorsal (cortical) patterning5 in the hypothalamus. In particular, loss of SLIT–ROBO signalling impaired both the production and positioning of periventricular dopamine neurons. Overall, we identify molecular principles that shape the developmental architecture of the hypothalamus and show how neuronal heterogeneity is transformed into a multimodal neural unit to provide virtually infinite adaptive potential throughout life.
DOI: 10.1038/s41586-020-2266-0
Source: https://www.nature.com/articles/s41586-020-2266-0
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
